VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival

Cancer Immunol Immunother. 2018 Jul;67(7):1113-1121. doi: 10.1007/s00262-018-2169-1. Epub 2018 May 8.

Abstract

Adaptive immune responses contribute to the pathogenesis of melanoma by facilitating immune evasion. V-domain Ig suppressor of T-cell activation (VISTA) is a potent negative regulator of T-cell function and is expressed at high levels on monocytes, granulocytes, and macrophages, and at lower densities on T-cell populations within the tumor microenvironment. In this study, 85 primary melanoma specimens were selected from pathology tissue archives and immunohistochemically stained for CD3, PD-1, PD-L1, and VISTA. Pearson's correlation coefficients identified associations in expression between VISTA and myeloid infiltrate (r = 0.28, p = 0.009) and the density of PD-1+ inflammatory cells (r = 0.31, p = 0.005). The presence of VISTA was associated with a significantly worse disease-specific survival in univariate analysis (hazard ratio = 3.57, p = 0.005) and multivariate analysis (hazard ratio = 3.02, p = 0.02). Our findings show that VISTA expression is an independent negative prognostic factor in primary cutaneous melanoma and suggests its potential as an adjuvant immunotherapeutic intervention in the future.

Keywords: Checkpoint inhibitor; Melanoma; Survival; Tumor microenvironment; Tumor-infiltrating lymphocytes; VISTA.

MeSH terms

  • B7 Antigens / immunology
  • B7 Antigens / metabolism*
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / mortality*
  • Melanoma / pathology
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / pathology
  • Survival Rate
  • Tumor Microenvironment

Substances

  • B7 Antigens
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • VSIR protein, human

Supplementary concepts

  • Melanoma, Cutaneous Malignant